Levetiracetam

LEVETIRACETAM — levetiracetam injection
Gland Pharma Limited

1 INDICATIONS AND USAGE

1.1 Partial-Onset Seizures

Levetiracetam in Sodium Chloride Injection is indicated as adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy.

1.2 Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy

Levetiracetam in Sodium Chloride Injection is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults with juvenile myoclonic epilepsy.

1.3 Primary Generalized Tonic-Clonic Seizures

Levetiracetam in Sodium Chloride Injection is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults with idiopathic generalized epilepsy.

1.4 Limitations of Use

Levetiracetam in Sodium Chloride Injection is an antiepileptic drug indicated for adult patients (16 years and older) when oral administration is temporarily not feasible.

2 DOSAGE AND ADMINISTRATION

2.1 General Information – Administration

Levetiracetam in Sodium Chloride Injection is for intravenous infusion only. It is available in the following concentrations: three single-dose 100 mL bags, each containing a different total dosage of levetiracetam (500 mg [5 mg/mL], 1,000 mg [10 mg/mL], or 1,500 mg [15 mg/mL]).

A single-dose bag should be administered intravenously over a 15-minute IV infusion period.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Levetiracetam in Sodium Chloride Injection should not be further diluted prior to use. Any unused portion of the Levetiracetam in Sodium Chloride Injection contents should be discarded.

2.2 Initial Exposure to Levetiracetam

Levetiracetam can be initiated with either intravenous or oral administration.
Partial-Onset Seizures

In clinical trials of oral levetiracetam, daily doses of 1,000 mg, 2,000 mg, and 3,000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose [see Clinical Studies (14.1)], a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1,000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1,000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3,000 mg. Doses greater than 3,000 mg/day have been used in open-label studies with levetiracetam tablets for periods of 6 months and longer. There is no evidence that doses greater than 3,000 mg/day confer additional benefit.
Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy

Treatment should be initiated with a dose of 1,000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1,000 mg/day every 2 weeks to the recommended daily dose of 3,000 mg. The effectiveness of doses lower than 3,000 mg/day has not been studied.

Primary Generalized Tonic-Clonic Seizures

Treatment should be initiated with a dose of 1,000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1,000 mg/day every 2 weeks to the recommended daily dose of 3,000 mg. The effectiveness of doses lower than 3,000 mg/day has not been adequately studied.

2.3 Switching to Intravenous Dosing


When switching from oral levetiracetam, the initial total daily intravenous dosage of levetiracetam should be equivalent to the total daily dosage and frequency of oral levetiracetam.

2.4 Switching to Oral Dosing


At the end of the intravenous treatment period, the patient may be switched to levetiracetam oral administration at the equivalent daily dosage and frequency of the intravenous administration.

2.5 Adult Patients with Impaired Renal Function

Levetiracetam dosing must be individualized according to the patient’s renal function status. Recommended doses and adjustment for dose for adults are shown in Table 1. To use this dosing table, an estimate of the patient’s creatinine clearance (CLcr) in mL/min is needed.

Table 1: Dosing Adjustment Regimen for Adult Patients with Impaired Renal Function

Group Creatinine Clearance (mL/min) Dosage (mg) Frequency
Normal greater than 80 500 to 1,500 Every 12 hours
Mild 50 to 80 500 to 1,000 Every 12 hours
Moderate 30 to 50 250 to 750 Every 12 hours
Severe less than 30 250 to 500 Every 12 hours
ESRD patients using dialysis —- 500 to 1,000 1 Every 24 hours

1 Following dialysis, a 250 mg to 500 mg supplemental dose is recommended.

2.6 Compatibility with Other Antiepileptic Drugs


Levetiracetam in Sodium Chloride Injection is found to be physically compatible and chemically stable for at least 24 hours when mixed with lorazepam, diazepam, and valproate sodium and stored at controlled room temperature 15°C to 30°C (59°F to 86°F).

There are no data to support the physical compatibility of levetiracetam injection with antiepileptic drugs that are not listed above.

2.7 Discontinuation of Levetiracetam

Avoid abrupt withdrawal from levetiracetam in order to reduce the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.6)].

3 DOSAGE FORMS AND STRENGTHS

Injection: Levetiracetam in Sodium Chloride Injection is a clear, colorless solution packaged in a single-dose bag and available in three strengths:

  • 500 mg/100 mL (5 mg/mL): 500 mglevetiracetam in 0.82% sodium chloride
  • 1,000 mg/100 mL (10 mg/mL): 1,000 mg levetiracetam in 0.75% sodium chloride
  • 1,500 mg/100 mL (15 mg/mL): 1,500 mg levetiracetam in 0.54% sodium chloride

4 CONTRAINDICATIONS


Levetiracetam in Sodium Chloride Injection is contraindicated in patients with a hypersensitivity to levetiracetam. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.3)].

5 WARNINGS AND PRECAUTIONS

5.1 Psychiatric Reactions

In some patients levetiracetam causes behavioral abnormalities. The incidences of behavioral abnormalities in the myoclonic and primary generalized tonic-clonic seizure studies were comparable to those of the adult partial-onset seizure studies.

A total of 13.3% of adult levetiracetam-treated patients compared to 6.2% of placebo patients experienced non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, and nervousness).

A total of 1.7% of adult levetiracetam-treated patients discontinued treatment due to behavioral adverse events, compared to 0.2% of placebo patients. The treatment dose was reduced in 0.8% of adult levetiracetam-treated patients and in 0.5% of placebo patients.

One percent of adult levetiracetam-treated patients experienced psychotic symptoms compared to 0.2% of placebo patients.

Two (0.3%) adult levetiracetam-treated patients were hospitalized and their treatment was discontinued due to psychosis. Both events, reported as psychosis, developed within the first week of treatment and resolved within 1 to 2 weeks following treatment discontinuation.

The above psychiatric signs and symptoms should be monitored.

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